Adaptations to life in an estuary include a wide salinity tolerance, an extremely efficient osmoregulatory and respiratory physiology. These adaptive mechanisms are energy-consuming and relatively little data is available on the combined effects of abiotic stress factors on the energy metabolism of mysid shrimp. A new methodology (cellular energy allocation, CEA) to assess the energy budget was adopted for the estuarine crustacean Neomysis integer (Crustacea: Mysidacea). The biochemical composition of N. integer was determined: protein (7.39±1.81% wet weight), lipid (3.99±1.05% ww) and sugar (0.42±0.18% ww). To assess the effect of natural variability on the energy metabolic processes in N. integer, a fractional factorial test design was set up with different naturally (Westerscheldt estuary, The Netherlands) occurring combinations of temperature, salinity and dissolved oxygen. The different abiotic factors had no significant effect on the energy metabolism of N. integer within the tested range. Temperature explained the decrease in lipid, protein and total energy reserves. Temperature, in general, had the most adverse effect on the CEA. Salinity was the most important factor explaining the effects on sugar reserves, with higher salinities causing an increased sugar demand. By modeling the influence of these abiotic stresses on the energy metabolism (CEA) of N. integer, it will be possible to use the CEA as an ecologically relevant biomarker of exposure to pollutants in estuaries.